Typhoid fever is a bacterial infection that affects more than 21 million people annually in developing nations such as India, Pakistan, and Egypt with about 200,000 people dying from the disease. [1] Reports of typhoid fever in more developed industrialized nations has significantly decreased since the 1900s due to environmental sanitation improvements. However, in developing nations where poor sanitation systems are in place, typhoid fever is highly prevalent. Typhoid fever is a growing concern in such developing nations, in 2013 there were 11 million new cases reported worldwide and predominately affects children. [1] Typhoid fever is caused by the Salmonella typhi bacteria also known as Salmonella enterica serotype Typhi. Typhoid fever is spread by digestion of food or liquids contaminated by another individual with the disease. This disease can also be contracted through close contact with an infected individual. Individuals that are already infected can contaminate any surrounding water supply in a given area through stoop, which contains a significantly high concentration of the salmonella typhi bacteria that causes Typhoid fever. In addition, about 3-5% of people who have previously had typhoid fever are carriers of the bacteria and may become long term carriers though they present no symptoms of the disease. [3] As a result, typhoid fever is a very dangerous disease that affects many people in less developed parts of the world.
Figure 1. The map above shows the geographic areas around the world that are effected yearly by Typhoid fever. Taken from: https://www.sciencenews.org/article/cheap-shots-%E2%80%94-typhoid-vaccine-shows-broad-coverage
fever/basics/definition/con-20028553 (accessed Feb 1, 2017). 4. Reece, R. J.; Maxwell, A., DNA gyrase: structure and function. Critical Reviews in Biochemistry and Molecular Biology1991, 26, (3-4), 335–375.
Typhoid fever is caused by a strain of salmonella called salmonella typhi. In normal cells DNA replication occurs in the nucleus, and in bacteria the enzyme called DNA gyrase helps facilitate DNA replication by negatively supercoiling DNA in the presence of ATP. In addition, DNA gyrase is an enzyme that decatenates double stranded bacterial DNA circles and also serves to relieve strain on the DNA when it is unwound.
In order for bacteria such as salmonella typhi to grow and spread, the bacterial DNA must replicate. The enzyme DNA gyrase plays a very important role in bacterial DNA replication by functioning as the enzyme that cuts the circular DNA and helps facilitate the supercoiling process. [4] Therfore withought DNA gyrase the bacteria that causes Typhoid fever will not be able to survive, make this enzyme a prime target.
Figure 2. This is a visual ribbon representation of the enzyme DNA Gyrase from: http://aac.asm.org/content/55/10/4524/F2.expansion.html
Size: ~374 kDa is the molecular weight of DNA Gyrase [4]
Location: DNA Gyrase is only found in bacterial cells such as the bacteria that induces Typhoid fever. The enzyme DNA gyrase can be found inside the nucleus of cells or close to the genetic information, DNA, of the cell. [4]
Function in a normal cell:
DNA gyrase plays an important role in cells, and is vital for many cellular processes that include duplex DNA, replication, recombination, and transcription. [4] These processes all play a part in the cells of an organism functioning normally.
Drug Information:
Ciprofloxacin is an antibiotic that effectively fights many different types of bacterial infections including typhoid fever. The drug, Ciprofloxacin, is a part of a family of synthetic broad spectrum antibiotic drugs called quinolones. Ciprofloxacin is classified as a synthetic broad spectrum fluoroquinolones antibiotic that functions by preventing bacterial DNA from duplicating. Ciprofloxacin functions as an inhibitor to the enzyme DNA gyrase. The role of the antibiotic is to bind to and inhibit DNA gyrase in the bacterial salmonella typhi cells in infected individuals. The binding of Ciprofloxacin to DNA gyrase hinders bacterial replication as the enzyme becomes inactive and incapable of duplicating the bacterial DNA. Without DNA replication the bacterial cells can no longer survive and spread throughout the body. [4]
Schematic figure of drug:
Figure 3. Above is the chemical structure of the antibiotic, Ciprofloxacin from: https://pubchem.ncbi.nlm.nih.gov/compound/ciprofloxacin#section=Top
Ciprofloxacin is available in many different forms including immediate and extended release tablets, and oral suspension, and as a solution.
Side effects: Some mild side effects may include nausea, diarrhea, liver abnormalities, and rash is less than 2% of the population. [4]
Other names: Ciprofloxacin is the common name used for this antibiotic, but there are other names it can be identified with such as Cipro, Ciprobay, and Ciproxan.
Maker or company: Many different companies and suppliers provide Ciprofloxacin. Companies such as Yuhao Chemical, TargetMol, and Mcule.
Is it patented: Ciprofloxacin is a patented drug in many countries including the United States.
Origin:
Alternatives to this drug: There are some alternatives to Ciprofloxacin but are less effective. These alternatives include Ceftriaxone and Ofloxacin. These alternatives all function to kill bacterial infections in organisms but are not as effective as Ciprofloxacin to cure Typhoid fever. [2]
Miscellaneous: Ciprofloxacin is a relatively moderate priced antibiotic. This antibiotic costs on average 0.40 U.S dollars in the United States per dose. In 2010 about 20 million prescriptions for Ciprofloxacin were made making it the 5th most commonly prescribed drug in America. [4]
Other uses: Ciprofloxacin has many other uses such as the ability to fight many bacterial infections like urinary tract infections and help with bone and joint infections.
Disease/Drug of interest:
Motivation and Background:
Typhoid fever is a bacterial infection that affects more than 21 million people annually in developing nations such as India, Pakistan, and Egypt with about 200,000 people dying from the disease. [1] Reports of typhoid fever in more developed industrialized nations has significantly decreased since the 1900s due to environmental sanitation improvements. However, in developing nations where poor sanitation systems are in place, typhoid fever is highly prevalent. Typhoid fever is a growing concern in such developing nations, in 2013 there were 11 million new cases reported worldwide and predominately affects children. [1] Typhoid fever is caused by the Salmonella typhi bacteria also known as Salmonella enterica serotype Typhi. Typhoid fever is spread by digestion of food or liquids contaminated by another individual with the disease. This disease can also be contracted through close contact with an infected individual. Individuals that are already infected can contaminate any surrounding water supply in a given area through stoop, which contains a significantly high concentration of the salmonella typhi bacteria that causes Typhoid fever. In addition, about 3-5% of people who have previously had typhoid fever are carriers of the bacteria and may become long term carriers though they present no symptoms of the disease. [3] As a result, typhoid fever is a very dangerous disease that affects many people in less developed parts of the world.References:
- Web MD: Typhoid Fever Causes, Symptoms, Treatment and Vaccine. http://www.webmd.com/a-to-z-guides/typhoid-fever#1 (accessed Feb 1, 2017).
- Mayo Clinic: Typhoid Fever http://www.mayoclinic.org/diseasesconditions/typhoid
fever/basics/definition/con-20028553 (accessed Feb 1, 2017). 4. Reece, R. J.; Maxwell, A., DNA gyrase: structure and function. Critical Reviews in Biochemistry and Molecular Biology 1991, 26, (3-4), 335–375.External links:
3. National Institutes of Health: Typhoid Feverhttps://www.nichd.nih.gov/news/releases/Pages/typhoid_background.aspx
Target Information:
Typhoid fever is caused by a strain of salmonella called salmonella typhi. In normal cells DNA replication occurs in the nucleus, and in bacteria the enzyme called DNA gyrase helps facilitate DNA replication by negatively supercoiling DNA in the presence of ATP. In addition, DNA gyrase is an enzyme that decatenates double stranded bacterial DNA circles and also serves to relieve strain on the DNA when it is unwound.In order for bacteria such as salmonella typhi to grow and spread, the bacterial DNA must replicate. The enzyme DNA gyrase plays a very important role in bacterial DNA replication by functioning as the enzyme that cuts the circular DNA and helps facilitate the supercoiling process. [4] Therfore withought DNA gyrase the bacteria that causes Typhoid fever will not be able to survive, make this enzyme a prime target.
Size: ~374 kDa is the molecular weight of DNA Gyrase [4]
Location:
DNA Gyrase is only found in bacterial cells such as the bacteria that induces Typhoid fever. The enzyme DNA gyrase can be found inside the nucleus of cells or close to the genetic information, DNA, of the cell. [4]
Function in a normal cell:
DNA gyrase plays an important role in cells, and is vital for many cellular processes that include duplex DNA, replication, recombination, and transcription. [4] These processes all play a part in the cells of an organism functioning normally.
Drug Information:
Ciprofloxacin is an antibiotic that effectively fights many different types of bacterial infections including typhoid fever. The drug, Ciprofloxacin, is a part of a family of synthetic broad spectrum antibiotic drugs called quinolones. Ciprofloxacin is classified as a synthetic broad spectrum fluoroquinolones antibiotic that functions by preventing bacterial DNA from duplicating. Ciprofloxacin functions as an inhibitor to the enzyme DNA gyrase. The role of the antibiotic is to bind to and inhibit DNA gyrase in the bacterial salmonella typhi cells in infected individuals. The binding of Ciprofloxacin to DNA gyrase hinders bacterial replication as the enzyme becomes inactive and incapable of duplicating the bacterial DNA. Without DNA replication the bacterial cells can no longer survive and spread throughout the body. [4]Schematic figure of drug:
Formula:
C17H18FN3O3
Molecular weight:
331.347 g/mol
CAS Number:
85721-33-1
Delivery method:
Ciprofloxacin is available in many different forms including immediate and extended release tablets, and oral suspension, and as a solution.
Side effects:
Some mild side effects may include nausea, diarrhea, liver abnormalities, and rash is less than 2% of the population. [4]
Other names:
Ciprofloxacin is the common name used for this antibiotic, but there are other names it can be identified with such as Cipro, Ciprobay, and Ciproxan.
Maker or company:
Many different companies and suppliers provide Ciprofloxacin. Companies such as Yuhao Chemical, TargetMol, and Mcule.
Is it patented:
Ciprofloxacin is a patented drug in many countries including the United States.
Origin:
Alternatives to this drug:
There are some alternatives to Ciprofloxacin but are less effective. These alternatives include Ceftriaxone and Ofloxacin. These alternatives all function to kill bacterial infections in organisms but are not as effective as Ciprofloxacin to cure Typhoid fever. [2]
Miscellaneous:
Ciprofloxacin is a relatively moderate priced antibiotic. This antibiotic costs on average 0.40 U.S dollars in the United States per dose. In 2010 about 20 million prescriptions for Ciprofloxacin were made making it the 5th most commonly prescribed drug in America. [4]
Other uses:
Ciprofloxacin has many other uses such as the ability to fight many bacterial infections like urinary tract infections and help with bone and joint infections.